The arteriosclerotic damage of the arterial endothelium is initiated by risk factors like dyslipidemia, hypertension, diabetes mellitus, and smoking, which account for the majority of vascular morbidity and mortality. Interventional studies confirmed the causative role of hyperlipidemia, particularly of the modified LDL-cholesterol. A large number of epidemiological and interventional studies identified hypertension as another risk factor and showed the correlation between lowering blood pressure and the reduction in micro- and macrovascular complications. Diabetes mellitus decreases the life expectancy on average by 10 years, mainly due to cardiovascular disease. However, intensive control of blood glucose and blood pressure achieved a significant and clinically important reduction in death and complications related to diabetes. Smoking is a main risk factor for peripheral arterial disease and causes advanced arterial lesions in the younger people. Novel risk factors have been identified and contribute to the elucidation of the atherogenic process.